| Autor: |
Jiang S; Lindsley F. Kimball Research Institute, New York Blood Center, New York 10065, United States. sjiang@nybloodcenter.org, Tala SR, Lu H, Abo-Dya NE, Avan I, Gyanda K, Lu L, Katritzky AR, Debnath AK |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2011 Jan 27; Vol. 54 (2), pp. 572-9. Date of Electronic Publication: 2010 Dec 29. |
| DOI: |
10.1021/jm101014v |
| Abstrakt: |
On the basis of our earlier molecular docking analysis, we designed and synthesized 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones (12a-o) as HIV-1 entry inhibitors. Compounds 12a-o effectively inhibited infection by both laboratory-adapted and primary HIV-1 strains and blocked HIV-1 mediated cell-cell fusion and gp41 six-helix bundle formation. Molecular docking analyses on two highly active inhibitors, 12b, containing a carboxylic acid group, and 12m, containing a tetrazole group, indicated that they both fit snugly into the hydrophobic cavity of HIV-1 gp41 from which each has important ionic interactions with lysine 574 (K574). By contrast, molecular docking of 12i, a less active compound containing a pyrrole instead of a furan ring, indicated a completely different orientation from 12b and 12m and missed critical interactions. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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